August 26, 2013

New Puzzle Pieces In The Genetics Of Schizophrenia

Schizophrenia is a one of the most complex and devastating of the inherited mental disorders, and remains a significant public health concern. In a new study published in the journal Nature Genetics, an international team of researchers has identified 22 locations in the human genome that are involved in the development of the condition, including 13 that have been named for the very first time.

"If finding the causes of schizophrenia is like solving a jigsaw puzzle, then these new results give us the corners and some of the pieces on the edges," said Dr. Patrick F. Sullivan, a geneticist from the University of North Carolina and a study co-author. "We've debated this for a century, and we are now zeroing in on answers."

"This study gives us the clearest picture to date of two different pathways that might be going wrong in people with schizophrenia," he added. "Now we need to concentrate our research very urgently on these two pathways in our quest to understand what causes this disabling mental illness."

The study was based on a comprehensive genome-wide association study (GWAS) that included previous similar studies. The international team also looked at data from a Swedish national sample of over 5,000 schizophrenia cases and more than 6,200 controls. The total number of individuals included in the study was over 59,000.

One of the genetic mechanisms identified in the study included the genes CACNA1C and CACNB2, which are critic to the function of nerve cells. Another genetic mechanism, dubbed the ‘micro-RNA 137’ pathway, involves a known regulator of neuronal development.

"What's really exciting about this is that now we can use standard, off-the-shelf genomic technologies to help us fill in the missing pieces," Sullivan said. "We now have a clear and obvious path to getting a fairly complete understanding of the genetic part of schizophrenia. That wouldn't have been possible five years ago."

Another study published earlier this month by the journal Neuron, revealed that the psychotic symptoms experienced by those with schizophrenia are caused by a faulty switch in the brain that results in the confusion between internal thoughts and objective reality.

"In our daily life, we constantly switch between our inner, private world and the outer, objective world," Lena Palaniyappan, a Nottingham University psychiatrist who co-led the study, told Reuters. "This switching action is enabled by the connections between the insula and frontal cortex. (But) this switch process appears to be disrupted in patients with schizophrenia."

In the study, researchers used functional magnetic resonance imaging (fMRI) scans to contrast the brains of 35 healthy participants with those of 38 individuals with schizophrenia. The scientists were able to determine that healthy participants successfully used the connections between the insula and frontal cortex regions of the brain to switch between inner thoughts and outer reality, while the patients with schizophrenia were less able to shift activity to their frontal cortex.